scholarly journals Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1332
Author(s):  
Juan Sebastián Galecio ◽  
Elisa Escudero ◽  
José Joaquín Cerón ◽  
Giuseppe Crescenzo ◽  
Pedro Marín
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Apparent Volume ◽  
Wide Distribution ◽  
Volume Of Distribution ◽  
Time Data ◽  
Administration Time

A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

scholarly journals Pharmacokinetics of Gentamicin C1, C1a, and C2 in Beagles after a Single Intravenous Dose

2000 ◽  
Vol 44 (6) ◽  
pp. 1443-1447 ◽  
Author(s):  
Nina Isoherranen ◽  
Eran Lavy ◽  
Stefan Soback
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Time Data ◽  
Chromatography Method ◽  
The Mean ◽  
The Difference ◽  
Liquid Chromatography Method ◽  
Toxicological Significance

ABSTRACT The pharmacokinetics of gentamicin C1, C2, and C1a were studied in six beagles after administration of gentamicin at 4 mg/kg of body weight as a single intravenous bolus dose. Plasma concentrations of the gentamicin components were analyzed with a novel high-performance liquid chromatography method capable of identifying and quantifying each of the components. The pharmacokinetic analysis of the plasma concentration-versus-time data was performed using the noncompartmental approach. The results indicated significant differences in the pharmacokinetic characteristics between the gentamicin components C1, C1a, and C2. The mean residence times of gentamicin C1, C1a, and C2 were 81 ± 13, 84 ± 12, and 79 ± 13 min (mean ± standard deviation), respectively. The half-lives of the respective components were 64 ± 12, 66 ± 12 and 63 ± 12 min. Clearance (CL) of gentamicin C1, 4.62 ± 0.71 ml min−1 kg−1, was significantly higher (P = 0.0156) than CL of gentamicin C1a, 1.81 ± 0.26 ml min−1kg−1, and C2, 1.82 ± 0.25 ml min−1 kg−1. Similarly, the volume of distribution at steady state (V ss) of gentamicin C1, 0.36 ± 0.04 liter kg−1, was significantly higher (P = 0.0156) than the V ss of gentamicin C1a, 0.14 ± 0.01 liter kg−1, and C2, 0.15 ± 0.02 liter kg−1. Tissue binding was considered the most likely cause for the difference. The difference may have clinical and toxicological significance.

scholarly journals Pharmacokinetic Behavior and Pharmacokinetic/Pharmacodynamic Integration of Danofloxacin Following Single or Co-Administration with Meloxicam in Healthy Lambs and Lambs with Respiratory Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1190
Author(s):  
Mehmet Nihat Ural ◽  
Kamil Uney
Keyword(s):  
High Performance ◽  
Respiratory Infections ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Area Under The Curve ◽  
Lavage Fluid ◽  
Volume Of Distribution ◽  
E Coli ◽  
Elimination Half ◽  
Pharmacokinetic Behavior

The aim of this study was to determine the pharmacokinetics and pharmacodynamics of danofloxacin (DAN; 6 mg/kg) following subcutaneous administration alone or co-administration with meloxicam (MLX; 1 mg/kg) in healthy lambs and lambs with respiratory infections. The study was carried out using a total of four groups: HD (healthy; n = 6) and ID (infected; n = 7) groups who were administered DAN only, and HDM (healthy; n = 6) and IDM (infected; n = 7) groups who were administered DAN and MLX simultaneously. The plasma concentrations of DAN were determined using high-performance liquid chromatography–UV and analyzed by the non-compartmental method. DAN exhibited a similar elimination half-life in all groups, including both the healthy and infected lambs. The total clearance in the HDM, ID and IDM groups and volume of distribution in the HDM and IDM groups were significantly reduced. MLX in the IDM group significantly increased the area under the curve (AUC) and peak concentration (Cmax) of DAN compared to the HD group. The Mannheimia haemolytica, Escherichia coli, and Streptococcus spp. strains were isolated from bronchoalveolar lavage fluid samples of the infected lambs. When co-administration with meloxicam, DAN at a 6 mg/kg dose can provide optimum values of ƒAUC0–24/MIC (>56 h) and ƒCmax/MIC (>8) for susceptible M. haemolytica isolates with an MIC90 value of 0.25 µg/mL and susceptible E. coli isolates with an MIC value of ≤0.125 µg/mL.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

scholarly journals Plasma and tissue clindamycin antimicrobial activity after parenteral administration to cats under surgical conditions

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabrina Passini ◽  
Laura Montoya ◽  
Martín Lupi ◽  
Paula Lorenzini ◽  
María Fabiana Landoni ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Dose Interval ◽  
Tissue Concentrations ◽  
Administration Routes ◽  
Infection Treatment ◽  
Plasma Concentration Ratio ◽  
Surgical Conditions

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.

scholarly journals Pharmacokinetics of danofloxacin in African catfish (Clarias gariepinus) after intravenous and intramuscular administrations

2019 ◽  
Vol 67 (4) ◽  
pp. 602-609
Author(s):  
Mohamed Aboubakr ◽  
Ahmed Soliman
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Clarias Gariepinus ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
African Catfish ◽  
Caudal Vein ◽  
Group 2 ◽  
Total Body ◽  
The Right

The plasma pharmacokinetics of danofloxacin was studied in healthy African catfish (Clarias gariepinus) following a single intravenous (IV) and intramuscular (IM) administration of 10 mg/kg at 22 °C. Catfish were divided into two groups (each group containing 78 fish), then danofloxacin mesylate (10 mg/kg) was administered IV (into the caudal vein) in Group 1 and IM (into the right epaxial muscle) in Group 2, and blood was obtained from the caudal vein before (0 h) and after (0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h) of drug administration. High-performance liquid chromatography was used for the determination of plasma concentration, and a non-compartmental model was used for the analysis of pharmacokinetic parameters. After IV administration, elimination half-life (t1/2λz, 24.49 h), mean residence time (MRT, 30.14 h), volume of distribution at steady state (Vdss, 1.07 L/kg) and total body clearance (CLT, 0.035 L/h/kg) were determined. After IM administration, t1/2λz, MRT, peak concentration (Cmax), time to reach Cmax and bioavailability were 47.64 h, 61.06 h, 5.22 µg/mL, 1 h and 67.12%, respectively. After IM administration, danofloxacin showed good bioavailability and long t1/2λz. The favourable pharmacokinetic characteristics after IM administration support the use of danofloxacin for the treatment of susceptible bacterial infections in catfish.

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

1994 ◽  
Vol 12 (9) ◽  
pp. 1902-1909 ◽  
Author(s):  
D R Budman ◽  
L N Igwemezie ◽  
S Kaul ◽  
J Behr ◽  
S Lichtman ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Water Soluble ◽  
High Dose ◽  
Maximum Plasma ◽  
Rapid Infusion ◽  
Etoposide Phosphate

PURPOSE To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

scholarly journals Analgesic and Nonanalgesic Effects of Intravenous Hydromorphone - Relation to Plasma Concentrations in Healthy Volunteers

1996 ◽  
Vol 1 (2) ◽  
pp. 86-92 ◽  
Author(s):  
D Westerling ◽  
H Bjork ◽  
P Svedman ◽  
P Hoglund
Keyword(s):  
Healthy Volunteers ◽  
Analgesic Effect ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Systemic Clearance ◽  
The Third ◽  
Elimination Half ◽  
Pressure Pain Thresholds ◽  
Saliva Production

OBJECTIVE:To investigate the analgesic and nonanalgesic effects and the pharmacokinetics of an intravenous infusion of 2 mg hydromorphone over 20 mins.DESIGN:Open study.SUBJECTS:Twelve healthy volunteers.MEASUREMENTS:The analgesic effect of hydromorphone was evaluated serially using pressure pain thresholds (PPTs) measured on the third fingers and toes. The nonanalgesic effects of hydromorphone were measured as miosis, decrease of saliva production and central nervous effects such as euphoria/dysphoria, nausea, headache, fatigue and feeling of heaviness. Plasma concentration of hydromorphone was measured using high performance liquid chromatography.RESULTS:PPTs were significantly increased compared with baseline levels for up to 2 h after the infusion of hydromorphone. Significant miosis and reduction of saliva production were registered up to 6 h after drug administration. Fatigue and heaviness were reported by all subjects. In the studied opioid-naive subjects, the hydromorphone-induced analgesic effect was of shorter duration than the studied nonanalgesic effects. The terminal elimination half-life of hydromorphone was 1.87±0.4 h (± SD) (95% CI 1.61 to 2.13), systemic clearance was 1.81±0.25 L/min (95% CI 1.65 to 1.97) and volume of distribution was 4.15±0.86 L/kg (95% CI 3.6 to 4.71).CONCLUSION:Analgesia and nonanalgesic effects appear to be well correlated with the plasma concentrations of the hydromorphone.

The disposition of TCNU (tauromustine) in human malignant glioma: pharmacokinetic studies and clinical implications

1990 ◽  
Vol 72 (5) ◽  
pp. 721-725 ◽  
Author(s):  
Ian R. Whittle ◽  
Janet S. MacPherson ◽  
J. Douglas Miller ◽  
John F. Smyth
Keyword(s):  
Malignant Glioma ◽  
High Performance ◽  
Peak Plasma ◽  
Linear Regression Analysis ◽  
Plasma Concentrations ◽  
Tissue Level ◽  
Pharmacokinetic Studies ◽  
Tissue Concentrations ◽  
Content Type ◽  
Chromatography Analysis

✓ Tauromustine (TCNU), 130 mg/sq m, was administered intraoperatively by nasogastric tube to 10 patients with malignant glioma (seven glioblastomas and three anaplastic astrocytomas). High-performance liquid chromatography analysis of 32 tumor specimens for TCNU revealed that tissue concentrations ranged from 0 to 554 ng/gm; TCNU was not detected in necrotic regions of the tumor. Levels of TCNU in brain adjacent to tumor were similar to those recorded within the gliomas (range 0 to 635 ng/gm). The variability in the tissue level of TCNU was partly attributable to variable absorption of the drug, since peak plasma TCNU levels ranged from 164 to 3333 ng/ml. There were close quantitative and temporal relationships between the times of peak plasma levels (median 456 ng/ml at 45 minutes after administration), peak tumor levels (median 250 ng/gm tissue at 55 minutes), and brain adjacent to tumor levels (median 256 ng/gm tissue at 50 minutes). Linear regression analysis of the ratio between tissue and plasma TCNU levels at particular times after drug administration suggest that plasma concentrations can be used to estimate tissue concentrations. This study demonstrates that TCNU enters malignant glioma. In view of the activity of TCNU against a range of tumors, a full clinical evaluation of this new nitrosourea in malignant glioma seems justified.

Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers 

1999 ◽  
Vol 90 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Auke Dirk van der Meer ◽  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Jack W. van Kleef ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Unbound Fraction ◽  
Blood Samples ◽  
The Mean ◽  
The Difference

Background Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. Methods Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. Results The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P < 0.005). Conclusions The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

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